Inside Health

Setback for Antibiotics as Heart Treatment

By LAWRENCE K. ALTMAN

Published: October 10, 2000

Taking an antibiotic for three months failed to reduce the risk of new heart attacks and death among people with coronary artery heart disease, a Utah study has found.

The study, which is being reported today, counters findings from two earlier, smaller studies from England and Argentina that found a benefit from a shorter course of an antibiotic.

The surprising findings from the earlier studies contributed to a widespread hope that antibiotics would be an effective therapy for coronary artery disease.

Despite the tentative nature of the findings, they led many cardiologists to prescribe such drugs for patients with coronary heart disease.

The new study suggests that antibiotic therapy is not justified for coronary artery disease, according to the authors of the Utah study and an expert who wrote an editorial about it. The two articles are being reported in Circulation, a scientific journal published by the American Heart Association.

Heart disease researchers, influenced by the recent finding that a bacterium known as Helicobacter pylori can cause stomach ulcers, have been paying more attention to the importance of inflammation in coronary artery disease.

The inflammation hints that bacteria and other infectious agents may be important in initiating or aggravating coronary artery disease, which is the underlying disorder that leads to heart attacks.

Heart disease is the leading cause of death in the United States and most other developed countries.

The inflammation research and the importance of the tantalizing findings from the shorter course of an antibiotic in the British trial, published in 1997, led the Utah researchers to undertake the study using more intensive antibiotic therapy, said Dr. Joseph B. Muhlestein. He led the team of researchers who conducted the study at the LDS Hospital and University of Utah in Salt Lake City.

Findings from two other large, long-term studies should provide more definitive answers about a possible infectious cause of heart disease. But the findings are not expected until late 2003.

Participants in the earlier British study took the same antibiotic, azithromycin, that was used in the Utah study. Azithromycin is effective against against Chlamydia pneumoniae, which is known to cause bronchitis and pneumonia. Scientists have accumulated considerable evidence linking chronic infections, particularly from C. pneumoniae, to a role in coronary artery disease.

The Argentinian study used a different antibiotic, roxithromycin, which is also effective.

Studies have shown that 50 percent to 70 percent of adults have been infected with C. pneumoniae at some time in their lives. At least 50 studies have found C. pneumoniae in the fatty plaques that narrow the coronary arteries that nourish the heart. But the presence of C. pneumoniae in the plaques is not enough to prove it causes coronary artery disease or heart attacks.

Such proof would be difficult and require evidence from many studies, Dr. J. Thomas Grayston of the University of Washington in Seattle, wrote in the editorial. Dr. Grayston is a pioneer in chlamydia research.

Dr. Muhlestein's team said reports of the earlier studies ''appear to be overly enthusiastic.'' But his Utah team said that because none of the studies were definitive, the possibility of antibiotic benefit for heart patients ''deserves further testing.''

The Utah researchers and Dr. Grayston stressed that the role of infections in producing heart attacks remained an area of legitimate research.

The Utah study was designed to detect striking benefits from azithromycin, but its statistical power was too weak to detect a more modest benefit. Thus, there is a need for larger, longer-term studies to determine whether antibiotics can produce a modest reduction in heart attacks, Dr. Muhlestein's team said.

The Utah study involved 302 people who had blood tests that showed they had been infected by C. pneumoniae. Of these, 150 took azithromycin and 152 a placebo, or dummy pill, for purposes of scientific comparison. The participants agreed to allow the choice to be made by lot.

The participants took two azithromycin or placebo pills each day for three days and then two pills once a week for three months. The researchers followed all 302 participants for two years. After six months, 9 who took azithromycin had heart attacks, strokes or died, compared with 7 who took the placebo. Then from 6 to 24 months, the figures were 13 among the azithromycin users and 18 for the placebo users. The difference was not statistically significant.

Dr. Muhlestein's team said its findings were consistent with three possibilities: C. pneumoniae does not cause coronary artery disease; azithromycin produces only a small benefit; or C. pneumoniae causes coronary artery disease but the wrong antibiotic was tested.